Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse.
Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse.
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DOI：
10.1016/j.jvs.2008.07.063
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发表时间：
2008-12
影响因子：
4.3
通讯作者：
Messina, Louis M.
中科院分区：
文献类型：
--
作者：
Yang, Yagai;Tang, Gale;Yan, Jinglian;Park, Brian;Hoffman, Ari;Tie, Guodong;Wang, Rong;Messina, Louis M.
目前大多数后肢缺血的动物模型使用急性动脉闭塞，其不能准确地反映人类逐渐动脉闭塞的发病机制。因此，我们开发了第一个逐渐动脉闭塞的小鼠模型，并测试了调节血流恢复的机制严重依赖于动脉闭塞率的假设。通过在左股动脉近端和远端放置Ameroid缩窄器，并结扎股动脉分支（n=36）来诱导动脉逐渐闭塞。通过切除左股动脉实现急性动脉闭塞（n=36）。采用激光多普勒成像技术研究血流恢复情况。通过定量真实的时间PCR评估这两种模型之间的差异基因表达。通过免疫组织化学测定炎症和祖细胞募集。我们发现，慢性和急性股动脉闭塞后，缺氧相关基因在小腿显著增加，而在大腿没有显著增加（p<0.05）。仅在急性股动脉闭塞后，剪切应力依赖基因和炎症基因在大腿中立即上调（p<0.05）。这些基因表达的差异与SDF-1α表达增加、巨噬细胞和血管细胞的募集以及急性动脉闭塞后比逐渐动脉闭塞后更高的血流恢复一致（p<0.05）。这是第一项研究表明，调节血流恢复的机制严重依赖于动脉闭塞的速度。这种渐进性动脉闭塞的新模型可能更接近于人类疾病，并可能为创造新的分子疗法提供更准确的机制见解。
Most current animal models of hindlimb ischemia use acute arterial occlusion that does not accurately reflect the pathogenesis of gradual arterial occlusion in humans. We therefore developed the first mouse model of gradual arterial occlusion and tested the hypothesis that the mechanisms regulating blood flow recovery are critically dependent on the rate of arterial occlusion. Gradual arterial occlusion was induced by placing ameroid constrictors on the proximal and distal left femoral artery, and ligating the femoral arterial branches (n=36). Acute arterial occlusion was accomplished by excising the left femoral artery (n=36). The blood flow recovery was studied by laser Doppler imaging. Differential gene expression between these two models was assessed by quantitative real time PCR. Inflammatory and progenitor cells recruitment were determined by immunohistochemistry. We found that hypoxia-related genes increased significantly in the calf, but not in the thigh, after gradual and acute femoral arterial occlusion (p<0.05). Shear-stress dependent genes and inflammatory genes were upregulated immediately in the thigh only after acute femoral arterial occlusion (p<0.05). These differences in gene expression were consistent with increased SDF-1α expression, recruitment of macrophages and hemangiocytes, and higher blood flow recovery after acute arterial occlusion than after gradual arterial occlusion (p<0.05). This is the first study to show the mechanisms that regulate blood flow recovery are critically dependent on the rate of arterial occlusion. This novel model of gradual arterial occlusion may more closely resemble the human diseases, and may provide more accurate mechanistic insights for creating novel molecular therapies.
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影响因子：
4.3
作者：
Deindl, E;Boengler, K;Schaper, W
通讯作者：
Schaper, W
影响因子：
2.2
作者：
Brevetti, LS;Paek, R;Messina, LM
通讯作者：
Messina, LM
DOI：
10.1016/j.jtcvs.2004.02.036
发表时间：
2004-10-01
影响因子：
6
作者：
Schalch, P;Patejunas, G;Rosengart, TK
通讯作者：
Rosengart, TK
影响因子：
4.3
作者：
Tang, GL;Chang, DS;Messina, LM
通讯作者：
Messina, LM
影响因子：
--
作者：
KUCHAN, MJ;JO, H;FRANGOS, JA
通讯作者：
FRANGOS, JA